Race, ethnicity, ancestry, and aspects that impact HLA data and matching for transplant.

Race, ethnicity, and ancestry are terms that are often misinterpreted and/or used interchangeably. There is lack of consensus in the scientific literature on the definition of these terms and insufficient guidelines on the proper classification, collection, and application of this data in the scientific community. However, defining groups for human populations is crucial for multiple healthcare applications and clinical research. Some examples impacted by population classification include HLA matching for stem-cell or solid organ transplant, identifying disease associations and/or adverse drug reactions, defining social determinants of health, understanding diverse representation in research studies, and identifying potential biases. This article describes aspects of race, ethnicity and ancestry information that impact the stem-cell or solid organ transplantation field with particular focus on HLA data collected from donors and recipients by donor registries or transplant centers.

Estimating dental age of New Zealand juveniles and subadults using Demirjian's method.

Reference data for dental age estimate is sparse in New Zealand (NZ), with only two contemporary studies. Te Moananui et al. (J For Sci. 53(2), 2008) presented modified Demirjian percentile curves to estimate dental age of Pasifika, Maori, and European males and females (n = 1383), while Timmins et al. (Forensic Sci Med Pathol. 8:101-8, 2012) found the Demirjian method (1973) was valid for a smaller sample (n = 200) of unknown ancestry. The study presented here sought to validate the Demirjian and the Te Moananui methods for a sample of the NZ population of unknown ancestry and a subgroup of known ancestry i.e., Pasifika, Maori and European, for males and females. The Demirjian method (1976) was applied to the current study's sample consisting of 3523 individuals aged 4 to < 20 years. The seven left mandibular teeth (third molar excluded) and tooth scores were summed for each individual, with the Te Moananui methods applied to this subgroup. The results revealed these methods to be less than ideal for estimating dental age of the NZ sample, for both males and females. The probit regression form of Transition Analysis (TA) was employed to calculate the mean age entering each tooth stage, for the seven teeth, to reduce age mimicry that is commonly associated with traditional regression analysis. TA results revealed Pasifika and Maori individuals to be more advanced than Caucasian individuals. The sex groups were also compared to the mean ages presented by Demirjian and Levesque with mixed results (J Dent Res. 59(7):1110-22, 1980), highlighting the need for more research in this area.

On the effect heterogeneity of established disease susceptibility loci for Alzheimer's disease across different genetic ancestries.

INTRODUCTION: Genome-wide association studies have identified numerous disease susceptibility loci (DSLs) for Alzheimer's disease (AD). However, only a limited number of studies have investigated the dependence of the genetic effect size of established DSLs on genetic ancestry. METHODS: We utilized the whole genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP) including 35,569 participants. A total of 25,459 subjects in four distinct populations (African ancestry, non-Hispanic White, admixed Hispanic, and Asian) were analyzed. RESULTS: We found that nine DSLs showed significant heterogeneity across populations. Single nucleotide polymorphism (SNP) rs2075650 in translocase of outer mitochondrial membrane 40 (TOMM40) showed the largest heterogeneity (Cochran's Q = 0.00, I2 = 90.08), followed by other SNPs in apolipoprotein C1 (APOC1) and apolipoprotein E (APOE). Two additional loci, signal-induced proliferation-associated 1 like 2 (SIPA1L2) and solute carrier 24 member 4 (SLC24A4), showed significant heterogeneity across populations. DISCUSSION: We observed substantial heterogeneity for the APOE-harboring 19q13.32 region with TOMM40/APOE/APOC1 genes. The largest risk effect was seen among African Americans, while Asians showed a surprisingly small risk effect.

The impact of telomere length on prostate cancer aggressiveness, genomic instability and health disparities.

The telomere repetitive TTAGGG motif at the ends of chromosomes, serves to preserve genomic integrity and chromosomal stability. In turn, genomic instability is a hallmark of cancer-implicating telomere disturbance. Prostate cancer (PCa) shows significant ancestral disparities, with men of African ancestry at the greatest risk for aggressive disease and associated genomic instability. Yet, no study has explored the role of telomere length (TL) with respect to ancestrally driven PCa health disparities. Patient- and technically-matched tumour-blood whole genome sequencing data for 179 ancestrally defined treatment naïve PCa patients (117 African, 62 European), we assessed for TL (blood and tumour) associations. We found shortened tumour TL to be associated with aggressive PCa presentation and elevated genomic instabilities, including percentage of genome alteration and copy number gains, in men of African ancestry. For European patients, tumour TL showed significant associations with PCa driver genes PTEN, TP53, MSH2, SETBP1 and DDX11L1, while shorter blood TL (< 3200 base pairs) and tumour TL (< 2861 base pairs) were correlated with higher risk for biochemical recurrence. Concurring with previous studies linking TL to PCa diagnosis and/or prognosis, for the first time we correlated TL differences with patient ancestry with important implications for future treatments targeting telomere dysfunction.

The socio-colonial history of Surinamese surnames applied to a validated surname list to identify ancestry in health research.

Around half of the population of Suriname, who are mainly of African and South Asian descent, migrated to the Netherlands at the end of the previous century, where they face higher perinatal and maternal mortality and up to 5 years lower life expectancy than European-Dutch. Analyses by ancestry are needed to address these inequalities, but the law prohibits registration by ancestry. Therefore, a list of Surinamese surnames was compiled and validated to identify the largest groups, African-Surinamese or South Asian-Surinamese ancestry in health research. A complete database of Surinamese surnames was provided by the National Population Registry of Suriname. Surname recognition by researchers of Surinamese ancestry was used. Disagreement was resolved using historical registers and through discussion. The list was further validated against contemporary lists of Surinamese surnames with self-defined ancestry, obtained during population and clinical studies in Suriname and the Netherlands. All 71,529 Surinamese surnames were encoded, as African-Surinamese (34%), South Asian-Surinamese (18%), Brazilian or other Iberian (17%), Indonesian-Surinamese (13%), Chinese-Surinamese (5%), First Nation (2%), and other (10%). Compared to self-defined ancestry, South Asian-Surinamese surname coding had 100% sensitivity, 99.8% specificity, and 99.9% accuracy. For African-Surinamese, who may have Dutch surnames, these values depended on geocoding. With a known Surinamese origin, sensitivity, specificity, and accuracy were, respectively, 97.3%, 100%, and 98.6%, but without this information, there was interference of African-Surinamese with European-Dutch surnames in the Dutch validation sample. In conclusion, the Surinamese Surname List has a high accuracy in identifying persons of Surinamese ancestry. This quick, inexpensive, and nonintrusive method, which is unaffected by response bias, might be a valuable tool in public health research to help address the profound health disparities by ancestry.

The Trotter collection: A review of Mildred Trotter's hair research and an update for studies of human variation.

OBJECTIVES: Mildred Trotter was an anatomist and physical anthropologist whose studies on hair morphology, growth, somatic distribution, and trait relationships to age and ethnogeographic population were foundational to the field of microscopical hair analysis. The collection of human hair samples she assembled for her research has been an underutilized resource for studies on human hair variation. We applied updated methods and reviewed Trotter's original data to reassess the relationship hair traits have to diverse population labels. METHODS: Hair form and pigmentation patterns were measured from a subset of the hair samples accumulated by Trotter and we compared our data to Trotter's original results. Variability in hair traits were tested within individuals, within populations, and among ethnogeographic groups. RESULTS: Measured hair cross-section dimensions and melanosome density and distribution revealed substantial variability within individuals and ethnogeographic populations. Hair traits were found to not be distinctly separable by ancestry but instead showed continuous variation across human populations. Trotter's measurements were precise and the dataset she compiled remains valid, though the conclusions should be reviewed in light of our current understanding of human variation. DISCUSSION: Our findings support moving away from categorical ancestry classifications and eliminating the use of outdated racial typologies in favor of more descriptive trait analysis. Detailed analysis of trait pattern distributions are presented that may be useful for future research on human variation. We point to the need for additional research on human variation and hair trait relationships with reference to known population affinity.

Genomic ancestry and cancer among Latin Americans.

Latin American populations, characterized by intricate admixture patterns resulting from the intermingling of ancestries from European, Native American (NA) Asian, and African ancestries which result in a vast and complex genetic landscape, harboring unique combinations of novel variants. This genetic diversity not only poses challenges in traditional population genetics methods but also opens avenues for a deeper understanding of its implications in health. In cancer, the interplay between genetic ancestry, lifestyle factors, and healthcare disparities adds a layer of complexity to the varying incidence and mortality rates observed across different Latin American subpopulations. This complex interdependence has been unveiled through numerous studies, whether conducted on Latin American patients residing on the continent or abroad, revealing discernible differences in germline composition that influence divergent disease phenotypes such as higher incidence of Luminal B and Her2 breast tumors, EGFR and KRAS mutated lung adenocarcinomas in addition to an enrichment in BRCA1/2 pathogenic variants and a higher than expected prevalence of variants in colorectal cancer associated genes such as APC and MLH1. In prostate cancer novel risk variants have also been solely identified in Latin American populations. Due to the complexity of genetic divergence, inputs from each individual ancestry seem to carry independent contributions that interplay in the development of these complex disease phenotypes. By understanding these unique population characteristics, genomic ancestries hold a promising avenue for tailoring prognostic assessments and optimizing responses to oncological interventions.

Sex differences in Alzheimer's disease blood biomarkers in a Caribbean population of African ancestry: The Tobago Health Study.

INTRODUCTION: Alzheimer's disease (AD) is increasing in the Caribbean, especially for persons of African ancestry (PAA) and women. However, studies have mostly utilized surveys without AD biomarkers. METHODS: In the Tobago Health Study (n = 309; 109 women, mean age 70.3 ± 6.6), we assessed sex differences and risk factors for serum levels of phosphorylated tau-181 (p-tau181), amyloid-beta (Aß)42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Blood samples were from 2010 to 2013 for men and from 2019 to 2023 for women. RESULTS: Women were more obese, hypertensive, and sedentary but reported less smoking and alcohol use than men (age-adjusted p < 0.04). Compared to men, women had worse levels of AD biomarkers, with higher p-tau181 and lower Aß42/40, independent of covariates (p < 0.001). In sex-stratified analyses, higher p-tau181 was associated with older age in women and with hypertension in men. GFAP and NfL did not differ by sex. DISCUSSION: Women had worse AD biomarkers than men, unexplained by age, cardiometabolic diseases, or lifestyle. Studying risk factors for AD in PAA is warranted, especially for women earlier in life.

MUSSEL: Enhanced Bayesian polygenic risk prediction leveraging information across multiple ancestry groups.

Polygenic risk scores (PRSs) are now showing promising predictive performance on a wide variety of complex traits and diseases, but there exists a substantial performance gap across populations. We propose MUSSEL, a method for ancestry-specific polygenic prediction that borrows information in summary statistics from genome-wide association studies (GWASs) across multiple ancestry groups via Bayesian hierarchical modeling and ensemble learning. In our simulation studies and data analyses across four distinct studies, totaling 5.7 million participants with a substantial ancestral diversity, MUSSEL shows promising performance compared to alternatives. For example, MUSSEL has an average gain in prediction R2 across 11 continuous traits of 40.2% and 49.3% compared to PRS-CSx and CT-SLEB, respectively, in the African ancestry population. The best-performing method, however, varies by GWAS sample size, target ancestry, trait architecture, and linkage disequilibrium reference samples; thus, ultimately a combination of methods may be needed to generate the most robust PRSs across diverse populations.

Demographic characteristics and epigenetic biological aging among post-9/11 veterans: Associations of DunedinPACE with sex, race, and age.

Measures of epigenetic aging derived from DNA methylation (DNAm) have enabled the assessment of biological aging in new populations and cohorts. In the present study, we used an epigenetic measure of aging, DunedinPACE, to examine rates of aging across demographic groups in a sample of 2,309 United States military veterans from the VISN 6 MIRECC's Post-Deployment Mental Health Study. As assessed by DunedinPACE, female veterans were aging faster than male veterans (ß = 0.39, 95 % CI [0.29, 0.48], p < .001), non-Hispanic Black veterans were aging faster than non-Hispanic White veterans (ß = 0.58, 95 % CI [0.50, 0.66], p < .001), and older veterans were biologically aging faster than younger veterans (ß = 0.21, 95 % CI [0.18, 0.25], p < .001). In secondary analyses, these differences in rates of aging were not explained by a variety of biopsychosocial covariates. In addition, the percentage of European genetic admixture in non-Hispanic Black veterans was not associated with DunedinPACE. Our findings suggest that female and non-Hispanic Black veterans are at greater risk of accelerated aging among post-9/11 veterans. Interventions that slow aging might provide relatively greater benefit among veterans comprising these at-risk groups.

Exploring cranial macromorphoscopic variation and classification accuracy in a South African sample.

To date South African forensic anthropologists are only able to successfully apply a metric approach to estimate population affinity when constructing a biological profile from skeletal remains. While a non-metric, or macromorphoscopic approach exists, limited research has been conducted to explore its use in a South African population. This study aimed to explore 17 cranial macromorphoscopic traits to develop improved methodology for the estimation of population affinity among black, white and coloured South Africans and for the method to be compliant with standards of best practice. The trait frequency distributions revealed substantial group variation and overlap, and not a single trait can be considered characteristic of any one population group. Kruskal-Wallis and Dunn's tests demonstrated significant population differences for 13 of the 17 traits. Random forest modelling was used to develop classification models to assess the reliability and accuracy of the traits in identifying population affinity. Overall, the model including all traits obtained a classification accuracy of 79% when assessing population affinity, which is comparable to current craniometric methods. The variable importance indicates that all the traits contributed some information to the model, with the inferior nasal margin, nasal bone contour, and nasal aperture shape ranked the most useful for classification. Thus, this study validates the use of macromorphoscopic traits in a South African sample, and the population-specific data from this study can potentially be incorporated into forensic casework and skeletal analyses in South Africa to improve population affinity estimates.

Large-scale genome-wide SNP analysis reveals the rugged (and ragged) landscape of global ancestry, phylogeny, and demographic history in chicken breeds. / å¤§è§„æ¨¡å ¨åŸºå› ç»„SNPåˆ†æžæ­ç¤ºäº†é¸¡å“ç§çš„å ¨çƒç¥–å ˆã€ç§ç¾¤å‘å±•å’Œç§ç¾¤åŽ†å²çš„å¤æ‚(å’Œå¤šæ ·)çš„é—ä¼ å›¾è°±.

The worldwide chicken gene pool encompasses a remarkable, but shrinking, number of divergently selected breeds of diverse origin. This study was a large-scale genome-wide analysis of the landscape of the complex molecular architecture, genetic variability, and detailed structure among 49 populations. These populations represent a significant sample of the world's chicken breeds from Europe (Russia, Czech Republic, France, Spain, UK, etc.), Asia (China), North America (USA), and Oceania (Australia). Based on the results of breed genotyping using the Illumina 60K single nucleotide polymorphism (SNP) chip, a bioinformatic analysis was carried out. This included the calculation of heterozygosity/homozygosity statistics, inbreeding coefficients, and effective population size. It also included assessment of linkage disequilibrium and construction of phylogenetic trees. Using multidimensional scaling, principal component analysis, and ADMIXTURE-assisted global ancestry analysis, we explored the genetic structure of populations and subpopulations in each breed. An overall 49-population phylogeny analysis was also performed, and a refined evolutionary model of chicken breed formation was proposed, which included egg, meat, dual-purpose types, and ambiguous breeds. Such a large-scale survey of genetic resources in poultry farming using modern genomic methods is of great interest both from the viewpoint of a general understanding of the genetics of the domestic chicken and for the further development of genomic technologies and approaches in poultry breeding. In general, whole genome SNP genotyping of promising chicken breeds from the worldwide gene pool will promote the further development of modern genomic science as applied to poultry.

Genetic ancestry and radical prostatectomy findings in Hispanic/Latino patients.

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

Generalizability of Tau and Amyloid Plasma Biomarkers in Alzheimer's Disease Cohorts of Diverse Genetic Ancestries.

Introduction: Plasma phosphorylated threonine-181 of Tau and amyloid beta are biomarkers for differential diagnosis and preclinical detection of Alzheimer disease (AD). Given differences in AD risk across diverse populations, generalizability of existing biomarker data is not assured. Methods: In 2,086 individuals of diverse genetic ancestries (African American, Caribbean Hispanic, and Peruvians) we measured plasma pTau-181 and Aß42/Aß40. Differences in biomarkers between cohorts and clinical diagnosis groups and the potential discriminative performance of the two biomarkers were assessed. Results: pTau-181 and Aß42/Aß40 were consistent across cohorts. Higher levels of pTau181 were associated with AD while Aß42/Aß40 had minimal differences. Correspondingly, pTau-181 had greater predictive value than Aß42/Aß40, however, the area under the curve differed between cohorts. Discussion: pTau-181 as a plasma biomarker for clinical AD is generalizable across genetic ancestries, but predictive value may differ. Combining genomic and biomarker data from diverse individuals will increase understanding of genetic risk and refine clinical diagnoses.

Genetic characterization of a captive marmoset (Callithrix jacchus) colony using genotype-by-sequencing.

The marmoset is a fundamental nonhuman primate model for the study of aging, neurobiology, and many other topics. Genetic management of captive marmoset colonies is complicated by frequent chimerism in the blood and other tissues, a lack of tools to enable cost-effective, genome-wide interrogation of variation, and historic mergers and migrations of animals between colonies. We implemented genotype-by-sequencing (GBS) of hair follicle derived DNA (a minimally chimeric DNA source) of 82 marmosets housed at the Southwest National Primate Research Center (SNPRC). Our primary goals were the genetic characterization of our marmoset population for pedigree verification and colony management and to inform the scientific community of the functional genetic makeup of this valuable resource. We used the GBS data to reconstruct the genetic legacy of recent mergers between colonies, to identify genetically related animals whose relationships were previously unknown due to incomplete pedigree information, and to show that animals in the SNPRC colony appear to exhibit low levels of inbreeding. Of the >99,000 single-nucleotide variants (SNVs) that we characterized, >9800 are located within gene regions known to harbor pathogenic variants of clinical significance in humans. Overall, we show the combination of low-resolution (sparse) genotyping using hair follicle DNA is a powerful strategy for the genetic management of captive marmoset colonies and for identifying potential SNVs for the development of biomedical research models.

Features Associated with Visible Lamina Cribrosa Pores in Individuals of African Ancestry with Glaucoma: Primary Open-Angle African Ancestry Glaucoma Genetics (POAAGG) Study.

There are scarce data regarding the rate of the occurrence of primary open-angle glaucoma (POAG) and visible lamina cribrosa pores (LCPs) in the eyes of individuals with African ancestry; the potential impact of these features on disease burden remains unknown. We recruited subjects with POAG to the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Through regression models, we evaluated the association between the presence of LCPs and various phenotypic features. In a multivariable analysis of 1187 glaucomatous eyes, LCPs were found to be more likely to be present in eyes with cup-to-disc ratios (CDR) of ≥0.9 (adjusted risk ratio (aRR) 1.11, 95%CI: 1.04-1.19, p = 0.005), eyes with cylindrical-shaped (aRR 1.22, 95%CI: 1.11-1.33) and bean pot (aRR 1.24, 95%CI: 1.13-1.36) cups versus conical cups (p < 0.0001), moderate cup depth (aRR 1.24, 95%CI: 1.06-1.46) and deep cups (aRR 1.27, 95%CI: 1.07-1.50) compared to shallow cups (p = 0.01), and the nasalization of central retinal vessels (aRR 1.33, 95%CI: 1.23-1.44), p < 0.0001). Eyes with LCPs were more likely to have a higher degree of African ancestry (q0), determined by means of SNP analysis (aRR 0.96, 95%CI: 0.93-0.99, p = 0.005 for per 0.1 increase in q0). Our large cohort of POAG cases of people with African ancestry showed that LCPs may be an important risk factor in identifying severe disease, potentially warranting closer monitoring by physicians.

Towards fair and clinically relevant polygenic predictions.

Lennon et al. recently proposed a clinical polygenic score (PGS) pipeline as part of the Electronic Medical Records and Genomics (eMERGE) network initiative. In this spotlight article we discuss the broader context for the use of PGS in preventive medicine and highlight key limitations and challenges facing their inclusion in prediction models.

Indigenous DNA as a metaphor: Nation-building and scientific debates on the rediscovery of Taiwanese ancestry.

In this paper, I investigate the co-production of genetic research and national politics in post-martial law Taiwan. This entails analyzing two co-produced phenomena: the nationalization of biomedicine-in which the national discourse over racial/ethnic categories and ancestral origin increasingly shapes scientists' biomedical research; and the biomedicalization of the nation-in which people in public discourse increasingly use biomedical categories in characterizing national differences and identities. I analyze how the production and representation of scientific knowledge of the ancestral origins and genetic make-up of Taiwan have been embedded in Taiwanese politics. This includes the emergence of a new categorization into four great ethnic groups, multiculturalism, and the assertion of a distinct Taiwanese national identity, particularly in response to the People's Republic of China's claims of common ancestry. I also examine how the scientific findings produced in the lab have spilled out into both Taiwan and China through journals, media, history textbooks, and public disputes since the 1990s and brought about significant social impact.

The power of representation: Statistical analysis of diversity in US Alzheimer's disease genetics data.

INTRODUCTION: Alzheimer's disease (AD) is a complex disease influenced by genetics and environment. More than 75 susceptibility loci have been linked to late-onset AD, but most of these loci were discovered in genome-wide association studies (GWAS) exclusive to non-Hispanic White individuals. There are wide disparities in AD risk across racially stratified groups, and while these disparities are not due to genetic differences, underrepresentation in genetic research can further exacerbate and contribute to their persistence. We investigated the racial/ethnic representation of participants in United States (US)-based AD genetics and the statistical implications of current representation. METHODS: We compared racial/ethnic data of participants from array and sequencing studies in US AD genetics databases, including National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) and NIAGADS Data Sharing Service (dssNIAGADS), to AD and related dementia (ADRD) prevalence and mortality. We then simulated the statistical power of these datasets to identify risk variants from non-White populations. RESULTS: There is insufficient statistical power (probability <80%) to detect single nucleotide polymorphisms (SNPs) with low to moderate effect sizes (odds ratio [OR]<1.5) using array data from Black and Hispanic participants; studies of Asian participants are not powered to detect variants OR <= 2. Using available and projected sequencing data from Black and Hispanic participants, risk variants with OR = 1.2 are detectable at high allele frequencies. Sample sizes remain insufficiently powered to detect these variants in Asian populations. DISCUSSION: AD genetics datasets are largely representative of US ADRD burden. However, there is a wide discrepancy between proportional representation and statistically meaningful representation. Most variation identified in GWAS of non-Hispanic White individuals have low to moderate effects. Comparable risk variants in non-White populations are not detectable given current sample sizes, which could lead to disparities in future studies and drug development. We urge AD genetics researchers and institutions to continue investing in recruiting diverse participants and use community-based participatory research practices.

Deconvoluting multi-person biological mixtures and accurate characterization and identification of separated contributors using non-targeted single-cell DNA sequencing.

The genetic characterization and identification of individuals who contributed to biological mixtures are complex and mostly unresolved tasks. These tasks are relevant in various fields, particularly in forensic investigations, which frequently encounters crime scene stains generated by more than one person. Currently, forensic mixture deconvolution is mostly performed subsequent to forensic DNA profiling at the level of the mixed DNA profiles, which comes with several limitations. Some previous studies attempted at separating single cells prior to forensic DNA profiling. However, these approaches are biased at selection of the cells and, due to their targeted DNA analysis on low template DNA, provide incomplete and unreliable forensic DNA profiles. We recently demonstrated the feasibility of performing mixture deconvolution prior to forensic DNA profiling through the utilization of a non-targeted single-cell transcriptome sequencing (scRNA-seq). In addition to individual-specific mixture deconvolution, this approach also allowed accurate characterisation of biological sex, biogeographic ancestry and individual identification of the separated mixture contributors. However, RNA has the forensic disadvantage of being prone to degradation, and sequencing RNA - focussing on coding regions - limits the number of single nucleotide polymorphisms (SNPs) utilized for genetic mixture deconvolution, characterization, and identification. These limitations can be overcome by performing single-cell sequencing on the level of DNA instead of RNA. Here, for the first time, we applied non-targeted single-cell DNA sequencing (scDNA-seq) by applying the scATAC-seq (Assay for Transposase-Accessible Chromatin with sequencing) technique to address the challenges of mixture deconvolution in the forensic context. We demonstrated that scATAC-seq, together with our recently developed De-goulash data analysis pipeline, is capable of deconvoluting complex blood mixtures of five individuals from both sexes with varying biogeographic ancestries. We further showed that our approach achieved correct genetic characterization of the biological sex and the biogeographic ancestry of each of the separated mixture contributors and established their identity. Furthermore, by analysing in-silico generated scATAC-seq data mixtures, we demonstrated successful individual-specific mixture deconvolution of i) highly complex mixtures of 11 individuals, ii) balanced mixtures containing as few as 20 cells (10 per each individual), and iii) imbalanced mixtures with a ratio as low as 1:80. Overall, our proof-of-principle study demonstrates the general feasibility of scDNA-seq in general, and scATAC-seq in particular, for mixture deconvolution, genetic characterization and individual identification of the separated mixture contributors. Furthermore, it shows that compared to scRNA-seq, scDNA-seq detects more SNPs from fewer cells, providing higher sensitivity, that is valuable in forensic genetics.